Escitalopram

Drug Levels and Effects:




Summary of Use during Lactation:


Escitalopram is the

S

-isomer of the antidepressant, citalopram. Limited information indicates that maternal doses of escitalopram up to 20 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Based on limited data, escitalopram appears to be preferable to racemic citalopram during breastfeeding because of the lower dosage and milk levels and general lack of adverse reactions in breastfed infants. One case of necrotizing enterocolitis was reported in an breastfed newborn whose mother was taking escitalopram during pregnancy and lactation, but causality was not established. Monitor the infant for drowsiness, especially in younger, exclusively breastfed infants and when using combinations of psychotropic drugs. Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding and may need additional breastfeeding support.


Drug Levels:


Escitalopram is the

S

-isomer of racemic citalopram which is metabolized to 2 metabolites, each having antidepressant activity considered to be about 13% that of citalopram.[1]

Maternal Levels.

Eight women taking escitalopram in an average dosage of 199 mcg/kg daily (10 to 20 mg daily) had 6 to 8 milk steady-state milk samples analyzed over the 24-hour interval after their single daily dose. The average dosage that an exclusively breastfed infant would receive was calculated to be 7.6 mcg/kg of escitalopram and 3 mcg/kg of desmethylcitalopram daily which were 3.9% and 1.7% of the maternal weight-adjusted dosages, respectively. The absolute dosage was about 40% less than a previous study by the same authors with racemic citalopram.[2]

A woman taking escitalopram had milk escitalopram concentrations measured twice. While taking a dosage of 5 mg daily, milk escitalopram was 24.9 mcg/L at 20 hours after the dose. While taking 10 mg escitalopram daily and valproic acid 1200 mg daily, milk escitalopram was 76.1 mcg/L at 15 hours after the dose. Using these two data points, the authors estimated that the infant received 5.1 and 7.7% of the maternal weight-adjusted dosage of escitalopram on these days, respectively.[3]

One woman was taking escitalopram 20 mg daily and reboxetine 4 mg daily orally while nursing her 9.5-month-old infant. She collected milk samples before each breastfeeding session over a 1-day period. The authors estimated that the infant would receive 4.6% of the maternal-weight-adjusted dosage of escitalopram plus desmethylescitalopram.[4]

Infant Levels

One study found that racemic citalopram serum levels in infants were determined by their CYP2C19 genotype, with slow metabolizers more likely to have detectable serum levels.[5] Pharmacogenetics likely plays a part in determining the exposure of breastfed infants to escitalopram also.

In 8 breastfed infants whose mothers were taking an average of 199 mcg/kg daily of escitalopram (10 or 20 mg daily), escitalopram and desmethylescitalopram were undetectable in the serum of 3 infants (<1 mcg/L). The drug and metabolite serum levels were less than 5 mcg/L in all the other infants. Their mothers' serum levels of the drug and metabolite averaged 24 and 20 mcg/L, respectively.[2]


Effects in Breastfed Infants:


Eight breastfed infants whose mothers were taking escitalopram in an average dose of 199 mcg/kg daily for postpartum depression were evaluated by a pediatric specialist using the Denver developmental scale. Their mothers had taken escitalopram for a median of 55 days postpartum (range 23 to 240 days). The infants' scores on this scale was 110% of normal.[2]

A woman began taking escitalopram 5 mg daily immediately after birth. Her dosage was increased to 10 mg daily and valproic acid 1200 mg daily was added by 7 weeks postpartum. Her breastfed infant was judged to be healthy and have normal neuropsychological development by a general practitioner at 7.5 weeks of age.[3]

One woman was taking escitalopram 20 mg daily and reboxetine 4 mg daily orally while nursing her infant (extent not stated). She had taken reboxetine for 1.5 months, but the start of her escitalopram therapy was not stated. At 9.5 months of age, her breastfed infant had normal weight gain and a Denver developmental score of 105% of chronological age.[4]

A mother began taking escitalopram 20 mg daily in the morning on day 15 postpartum. She exclusively breastfed her infant on demand. At 3 months of age, no adverse effects had been reported in the infant by his pediatrician.[6]

At 5 days of age, an infant was readmitted to the neonatal intensive care unit with a diagnosis of necrotizing enterocolitis. The infant had spent the first 2 days of life in intensive care because of respiratory distress. The infant's mother had taken escitalopram 20 mg daily throughout pregnancy and while breastfeeding (extent not stated). The authors hypothesized that escitalopram might have been responsible for the enterocolitis because of its effect on platelet aggregation.[7] The drug was possibly a cause of the reaction.

An uncontrolled online survey compiled data on 930 mothers who nursed their infants while taking an antidepressant. Infant drug discontinuation symptoms (e.g., irritability, low body temperature, uncontrollable crying, eating and sleeping disorders) were reported in about 10% of infants. Mothers who took antidepressants only during breastfeeding were much less likely to notice symptoms of drug discontinuation in their infants than those who took the drug in pregnancy and lactation.[8]


Possible Effects on Lactation:


The SSRI class of drugs, including escitalopram, can cause increased prolactin levels and galactorrhea in nonpregnant, nonnursing patients.[9][10][11][12][13][14] Euprolactinemic galactorrhea has also been reported.[15] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 takingfluoxetineand 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior compared to the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.[16]

A case control study compared the rate of predominant breastfeeding at 2 weeks postpartum in mothers who took an SSRI antidepressant throughout pregnancy and at delivery (n = 167) or an SSRI during pregnancy only (n = 117) to a control group of mothers who took no antidepressants (n = 182). Among the two groups who had taken an SSRI, 33 took citalopram, 18 took escitalopram, 63 tookfluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Among the women who took an SSRI, the breastfeeding rate at 2 weeks postpartum was 27% to 33% lower than mother who did not take antidepressants, with no statistical difference in breastfeeding rates between the SSRI-exposed groups.[17]


Alternate Drugs to Consider:


Nortriptyline,Paroxetine,Sertraline


References:


1. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID:15169695
2. Rampono J, Hackett LP, Kristensen JH et al. Transfer of escitalopram and its metabolite demethylescitalopram into breastmilk. Br J Clin Pharmacol. 2006;3:316-22. PMID:16934048
3. Castberg I, Spigset O. Excretion of escitalopram in breast milk. J Clin Psychopharmacol. 2006;26:536-8. PMID:16974204
4. Hackett LP, Ilett KF, Rampono J et al. Transfer of reboxetine into breastmilk, its plasma concentrations and lack of adverse effects in the breastfed infant. Eur J Clin Pharmacol. 2006;62:633-8. PMID:16699799
5. Berle JO, Steen VM, Aamo TO et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes. J Clin Psychiatry. 2004;65:1228-34. PMID:15367050
6. Gentile S. Escitalopram late in pregnancy and while breast-feeding. Ann Pharmacother. 2006;40:1696-7. PMID:16912243
7. Potts AL, Young KL, Carter BS, Shenai JP. Necrotizing enterocolitis associated with in utero and breast milk exposure to the selective serotonin reuptake inhibitor, escitalopram. J Perinatol. 2007;27:120-2. PMID:17262045
8. Hale TW, Kendall-Tackett K, Cong Z et al. Discontinuation syndrome in newborns whose mothers took antidepressants while pregnant or breastfeeding. Breastfeed Med. 2010;5:283-8. PMID:20807106
9. Arya DK, Taylor WS. Lactation associated withfluoxetinetreatment. Aust N Z J Psychiatry. 1995;29:697. Letter. PMID:8825840
10. Egberts ACG, Meyboom RHB, De Koning FHP et al. Non-puerperal lactation associated with antidepressant drug use. Br J Clin Pharmacol. 1997;44:277-81. PMID:9296322
11. Iancu I, Ratzoni G, Weitzman A et al. Morefluoxetineexperience. J Am Acad Child Adolesc Psychiatry. 1992;31:755-6. Letter. PMID:1644743
12. Gonzalez Pablos E, Minguez Martin L, Hernandez Fernandez M et al. [A clinical case of galactorrhoea after citalopram treatment]. Actas Esp Psiquiatr. 2001;29:414. PMID:11730581
13. Gulsun M, Algul A, Semiz UB et al. A case with euprolactinemic galactorrhea induced by escitalopram. Int J Psychiatry Med. 2007;37:275-8. PMID:18314855
14. Aggarwal A, Kumar R, Sharma RC, Sharma DD. Escitalopram induced galactorrhoea: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:557-8. PMID:20138200
15. Mahasuar R , Majhi P, Ravan JR. Euprolactinemic galactorrhea associated with use of imipramine and escitalopram in a postmenopausal woman. Gen Hosp Psychiatry. 2010;32:341.e11-3. PMID:20430243
16. Marshall AM, Nommsen-Rivers LA, Hernandez LL et al. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010;95:837-46. PMID:19965920
17. Gorman JR, Kao K, Chambers CD. Breastfeeding among women exposed to antidepressants during pregnancy. J Hum Lact. 2012;28:181-8. PMID:22344850



Substance Identification:




Substance Name:

Escitalopram

CAS Registry Number:

128196-01-0

Drug Class:


  • Antidepressants

  • Serotonin Uptake Inhibitors

  • Antidepressive Agents, Second-Generation


  • Administrative Information:




    LactMed Record Number:


    404


    Last Revision Date:


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